Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon
Autor: | Wout G.N. Mares, Marloes C. de Kok, Carla B.E.M. Vleugels-Simon, Theo M. de Kok, Marieke Pierik, Gunter G. C. Kuhnle, Jos C. S. Kleinjans, Marcel H. M. van Herwijnen, Kirstine M. Sveje, Leopold G.J.B. Engels, Ad A.M. Masclee, Dennie G. A. J. Hebels |
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Přispěvatelé: | Toxicogenomics, GezondheidsRisico Analyse en Toxicologie, Interne Geneeskunde, RS: NUTRIM - R2 - Gut-liver homeostasis, RS: GROW - School for Oncology and Reproduction |
Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Adult
Male Meat Colorectal cancer Colon Nitrosation Endogeny Biology Pharmacology Toxicology medicine.disease_cause Biological pathway Feces medicine Humans Carcinogen Aged Water General Medicine Middle Aged medicine.disease Inflammatory Bowel Diseases Diet Biochemistry Gene Expression Regulation Red Meat Consumption Red meat Female Genotoxicity Food Science DNA Damage |
Zdroj: | Food and Chemical Toxicology, 50(2), 95-103. Elsevier Science |
ISSN: | 0278-6915 |
Popis: | Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat consumption on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to genome-wide transcriptomic changes induced in colonic tissue. The intervention showed no effect on fecal NOC excretion but fecal water genotoxicity significantly increased in response to red meat intake. Colonic inflammation caused by inflammatory bowel disease, which has been suggested to stimulate endogenous nitrosation, did not influence fecal NOC excretion or fecal water genotoxicity. Transcriptomic analyses revealed that genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage repair, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated which are implicated in human CRC development. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a potentially increased CRC risk in humans. |
Databáze: | OpenAIRE |
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